Support is requested for a Keystone Symposia meeting entitled Genomic Instability and DNA Repair, organized by Daniel Durocher, Jiri Lukas and Agata Smogorzewska. The meeting will be held in Whistler, British Columbia, Canada from March 1-6, 2015. Far from being a single process, genome maintenance involves the integration of multiple DNA damage repair and signaling pathways that are deeply influenced by cell cycle progression, chromatin composition, gene transcription, genome organization and the differentiation state of the cell. Preservation of genomic integrity is of paramount importance for cellular homeostasis, organismal development and tumor suppression. Accordingly, defects in the pathways that signal and repair DNA damage cause pathologies that include cancer, neurological disorders, premature aging and immunodeficiency. Our understanding of genome maintenance in the context of the multitude of intracellular transactions remains woefully incomplete and topic sessions addressing this issue will comprise a major theme of the conference. The program uniquely connects fields that otherwise rarely meet on a single occasion and will cover genome stability, development, disease, telomere biology and stem cell function. The meeting will highlight the latest trends including how genomic technologies have revolutionized our view of genome integrity and led to the discovery of new types of genome rearrangements whose mechanistic underpinnings remain largely unknown. The unusually broad scope of the conference will bring together scientists operating at the leading edge of multiple disciplines ranging from basic cell biology to pre-clinical oncology. Interactions between junior and seasoned investigators, as well as interdisciplinary contacts, will be fostered through poster presentations, workshops and plenary sessions, some of which are shared with the concurrent Keystone Symposia meeting on DNA Replication and Recombination, which will focus on the highly complementary theme of repair in the setting of DNA replication. Genome instability often drives tumor formation and progression, thus faithful genome maintenance is essential for tumor suppression. Topics of this meeting range from the basic mechanism of DNA repair responsible for prevention of genome instability, to discussion of how DNA repair pathways impact clinical oncology including treatment and drug resistance. These are perfectly aligned with the mission of NCI.